Hypophysis is a small endocrine organ adjacent to the lower part of the diencephalon and plays a major role as a control center of various hormones. For example, it produces various pituitary hormones including adrenocorticotropic hormone (ACTH) which promotes production of corticosteroid essential for life support, growth hormone which promotes growth of children, and the like. Therefore, functional disorder of hypophysis causes severe systemic diseases. However, since hypophysis is formed through an extremely complicated developmental process in the embryo, it has been difficult to form hypophysis tissue from stem cells such as Embryonic Stem (ES) cells and the like.
The present inventors applied Serum-free Floating culture of Embryoid Body-like aggregates with quick reaggregation (SFEBq method) established as a method for efficiently differentiate nerve cells and retinal cells from pluripotent stem cells such as ES cells and the like, and succeeded in self-organization of the hypophysis from mouse ES cells in vitro (non-patent document 1). In this method, hedgehog signal is activated by culturing aggregates of mouse ES cells in suspension in a serum-free medium containing SAG, and hypothalamus and oral ectoderm are simultaneously formed in the aggregates, and the interaction thereof induces hypophysial placode formation and self organization of Rathke's pouch. It has been reported that endogenous BMP4 signal is required for hypophysial placode formation in this method based on inhibition experiments.